Microarray technology has developed to analyze a large number of complex biochemical reactions and systems in parallel. This technology provides a massively parallel form of analysis that increases data collection per unit time, decreases the overall time required for analysis, and uses smaller sample volumes. For these and other reasons, microarray technology is well suited for genomic research.
A microarray is a collection of chemical entities arranged on a substrate, which substrate is often glass, fused silica, borosilicate, quartz, soda lime glass, or some such similar substance. Each chemical entity occupies a predetermined position on the substrate. These positions are often referred to as “features”, “probes” or “probe regions” and may contain one to millions or more copies of a single chemical entity. These chemical entities may be of any number of classes of substances including, but not limited to nucleic acids, peptides, polysaccharides, carbohydrates, and phospholipids. After exposing the microarray to a sample under selected test conditions, scanning devices can examine locations in the microarray to determine whether sample molecules have interacted with probe regions at those locations.
Microarrays with a large number of probe regions may be manufactured by methods described in PCT Application WO 92/10092 or U.S. Pat. Nos. 5,143,854; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,445,934; 5,744,305; 5,800,992; 6,040,138; 6,040,193, all of which are hereby incorporated by reference in their entireties for all purposes. The probe regions may have side dimensions from about 10 μm to 100 μm. In some embodiments a probe region may be larger, such as about 1 cm across. In some applications, the substrate is a wafer with a synthesis area of about 110 mm×110 mm and may include large numbers of probe regions.
Wafers contain probe regions arranged in a plurality of probe arrays, such that each probe array comprises a specific subset of probe regions and is physically separated from the adjacent probe array(s). Typically, wafers containing the probe arrays are cut apart and packaged prior to being used for analysis. Therefore, probe arrays are separated by inert areas, commonly known as “alleys,” which allow space for a saw or similar tool to make cuts between the probe arrays. Each alley is commonly about 3 mm wide. Accordingly, the area occupied by alleys can be a significant part of the total area of a wafer, thereby reducing the area that may be used for probe arrays. Further, dicing and packaging probe arrays is expensive and wastes expensive substrate. However, it allows a plurality of samples to be tested on probe arrays produced from a single wafer.
It would be desirable to perform analyses with a plurality of samples on whole wafers, thereby avoiding the cost and wasted material involved with dicing and packaging probe arrays. However, if the wafer is not physically cut apart prior to analysis, other devices and methods are needed to isolate reaction sites on whole wafers.